Purpose. To review proved and experimental treatments for exudative and nonexudative complications of age-related macular degeneration (AMD), to consider the impact of current therapy on the structure of future clinical trials, and to consider the role of improved diagnostic imaging techniques on the effectiveness of current therapy as well as the structure of future clinical trials in AMD patients.
Results. Defining the cell biology of choroidal new vessel (CNV) formation and geographic atrophy will lead to identification of different biochemical pathways that are the target of AMD treatment. Many treatments and treatment combinations are under study for AMD, but all work through a finite number of pathways. Currently, the most effective proved therapy for AMD-associated CNVs is administered by repeated intravitreal injection of agents that inhibit vascular endothelial growth factor, e.g., ranibizumab. Improved drug delivery will enhance patient satisfaction and possibly will enhance the effectiveness and reduce the risk of current pharmacotherapy for AMD-associated CNVs. Combination therapy (e.g., verteporfin-photodynamic therapy + ranibizumab) appears to reduce the risk and enhance the effectiveness of CNV treatment compared with monotherapy with currently available agents. Improved noninvasive diagnostic imaging may lead to better visual outcomes with existing therapeutic modalities. Improved imaging also may alter favorably the design of future clinical trials for AMD-associated CNVs and thus reduce cost and increase the diversity of sight-saving treatments.
Conclusions. Delineation of the biochemical basis for CNV formation has led to development of pathway-based pharmacotherapy for AMD patients. Areas of investigation that will advance the field further include combination therapy, improved drug delivery, and improved noninvasive, high-resolution diagnostic imaging. The logistics of future clinical trials will be complicated by the need for an active treatment control group, more stringent definition of successful treatment, and the increased numbers of patients required for combination therapy studies.